Evaluation and treatment of rhinosinusitis with primary antibody deficiency in adults: Evidence-based review with recommendations.

BACKGROUND: There is clear evidence that the prevalence of primary antibody deficiency (PAD) is higher in patients with recurrent and chronic rhinosinusitis (CRS) than in the general population. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on rhinosinusitis with PAD, summarize the existing evidence, and provide recommendations on the evaluation and management of rhinosinusitis in patients with PAD. METHODS: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through August 2022. Studies on the evaluation and management of rhinosinusitis in PAD patients were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on the evaluation and management principles for PAD were generated. RESULTS: A total of 42 studies were included in this evidence-based review. These studies were evaluated on incidence of PAD in rhinosinusitis patients, incidence of rhinosinusitis in PAD patients, and on the different treatment modalities used and their outcome. The aggregate quality of evidence was varied across reviewed domains. CONCLUSION: Based on the currently available evidence, PAD can occur in up to 50% of patients with recalcitrant CRS. Despite the presence of multiple studies addressing rhinosinusitis and PAD, the level of evidence supporting different treatment options continues to be lacking. Optimal management requires a multidisciplinary approach through collaboration with clinical immunology. There is need for higher-level studies that compare different treatments in patients with PAD and rhinosinusitis.

Factors related to wellness and burnout in academic otolaryngology: A pre- and Post-COVID-19 analysis.

Objectives: Describe demographic and professional factors predictive of burnout in academic otolaryngology before and during the COVID-19 pandemic. Methods: In 2018 and 2020, cross-sectional surveys on physician wellness and burnout were distributed to faculty members of a single academic institution's otolaryngology department. Faculty were dichotomized into low and high burnout groups for 2018 (n = 8 high burnout, 19%) and 2020 (n = 11 high burnout, 37%). To identify protective factors against burnout, three semi-structured interviews were conducted with faculty that reported no burnout. Results: Forty-two participants (59%) in 2018 and 30 out of 49 participants (62%) in 2020 completed the survey. In multivariate analysis of 2018 survey data, full and associate professors had significantly lower odds of high burnout (OR 0.06, 95% CI 0.00-0.53; p = .03). Female gender was associated with increased in odds of high burnout (OR 15.55, 95% CI 1.86-231.74; p = .02). However, academic rank and gender did not remain independent predictors of high burnout in the 2020 survey. We identified significant differences in drivers of burnout brought on by the pandemic, including a shift from a myriad of work-related stressors in 2018 to a focus on patientcare and family obligations in 2020. Interview analysis identified three themes in faculty who reported no burnout: (1) focus on helping others, (2) happiness over compensation as currency, and (3) gratitude for the ability to have an impact. Conclusion: Approximately 20% of faculty reported high burnout before the pandemic, and this proportion nearly doubled during the pandemic. The risk factors and themes identified in this study may help academic otolaryngologists prevent burnout. Lay Summary: Factors driving burnout among academic otolaryngologists during the COVID-19 pandemic transitioned away from research, conferences, and work outside business hours toward family and patient responsibilities. Females report higher burnout and full professors report lower burnout. Level of evidence: III.

Are rhinitis and Eustachian tube dysfunction associated in United States adolescents?

OBJECTIVES: Despite longstanding clinical gestalt of a relationship between rhinitis and Eustachian tube dysfunction (ETD), population-level evidence supporting this connection is lacking, particularly among adolescents. We aimed to investigate the association between rhinitis and ETD in a nationally-representative sample of United States adolescents. METHODS: We performed cross-sectional analyses of 2005-2006 National Health and Nutrition Examination Survey data (n = 1955, ages 12-19). Rhinitis (self-reported hay fever and/or nasal symptoms in the past 12 months) was stratified as allergic (AR) or nonallergic rhinitis (NAR) based on serum IgE aeroallergen positivity. History of ear disease and procedures was recorded. Tympanometry was classified by type (A, B, C). Multivariable logistic regression was used to test the association of rhinitis and ETD. RESULTS: Among US adolescents, 29.4% reported rhinitis (NAR 38.9%, AR 61.1%), and 14.0% had abnormal tympanometry. Adolescents with rhinitis were more likely to report a history of ≥3 ear infections (NAR: OR 2.40, 95% CI: 1.72-3.34, p < 0.001; AR: OR 1.89, 95% CI: 1.21-2.95, p = 0.008) and tympanostomy tube placement (NAR: OR 3.53, 95% CI: 2.07-6.03, p < 0.001; AR: OR 1.91, 95% CI: 1.24-2.94, p = 0.006), compared to those without rhinitis. There was no association between rhinitis and abnormal tympanometry (NAR: p = 0.357; AR: p = 0.625). CONCLUSION: NAR and AR are both associated with history of frequent ear infections and tympanostomy tube placement in US adolescents, supporting an association with ETD. This association is strongest for NAR, suggesting that specific inflammatory mechanisms may be involved in this condition and potentially explaining why traditional therapies for AR are largely ineffective for ETD.

Climate change, the environment, and rhinologic disease.

BACKGROUND: The escalating negative impact of climate change on our environment has the potential to result in significant morbidity of rhinologic diseases. METHODS: Evidence based review of examples of rhinologic diseases including allergic and nonallergic rhinitis, chronic rhinosinusitis, and allergic fungal rhinosinusitis was performed. RESULTS: The lower socioeconomic population, including historically oppressed groups, will be disproportionately affected. CONCLUSIONS: We need a systematic approach to improve healthcare database infrastructure and funding to promote diverse scientific collaboration to address these healthcare needs.

Sublingual immunotherapy persistence and adherence in real-world settings: A systematic review.

BACKGROUND: Sublingual immunotherapy (SLIT) adherence in the literature is often evaluated in closely monitored trials that may impact patient behavior; real-world SLIT adherence is relatively unknown. This systematic review intends to assess SLIT adherence in studies that reflect real-world settings. METHODS: A literature search of PubMed, Embase, Cochrane, Web of Science, and Scopus for real-world studies examining SLIT adherence was performed. Monitored clinical trials were excluded. Paired investigators independently reviewed all articles. For this review, "persistence" was defined as continuing therapy and not being lost to follow-up and "adherence" as persistence in accordance with prescribed SLIT dose, dosing schedule, and duration. Article quality was assessed using a modified Newcastle-Ottawa scale and then converted to AHRQ standards (good, fair, and poor). RESULTS: The search yielded 1596 nonduplicate abstracts, from which 32 articles (n = 63,683 patients) met criteria. Twenty-six (81%) studies reported persistence rates ranging from 7.0% to 88.7%, and 18 (56%) reported adherence rates ranging from 9.6% to 97.0%. Twenty-one (66%) studies surveyed reasons for discontinuing SLIT. All studies were Oxford level of evidence 2b and of good (n = 12) to fair (n = 20) quality. CONCLUSION: Reported rates of real-world SLIT persistence and adherence varied widely by study methodology (e.g., follow-up duration, objective vs. subjective assessment). Studies with longer follow-up generally reported lower rates; 3-year persistence ranged from 7% to 59.0% and 3-year adherence from 9.6% to 49.0%. Future studies of SLIT adherence would benefit from following concordant definitions of persistence/adherence and standardized reporting metrics.

Systematic review of real-world persistence and adherence in subcutaneous allergen immunotherapy.

BACKGROUND: Given that subcutaneous immunotherapy (SCIT) adherence in the literature is often studied in closely monitored trials, few studies report real-world SCIT adherence. The purpose of this review is to assess SCIT adherence in real-world settings. METHODS: A literature search of PubMed, Embase, Cochrane Library, Web of Science, and Scopus for real-world studies examining SCIT adherence was performed. Paired investigators independently reviewed all articles. For this review, "persistence" was defined as continuing therapy and not being lost to follow-up after initiating SCIT, and "adherence" defined as persistence in accordance with prescribed SCIT dose, dosing schedule, and duration. Article quality was first assessed using a modified Newcastle-Ottawa scale and then converted to Agency for Healthcare Research and Quality standards (good, fair, and poor). RESULTS: The search yielded 1596 nonduplicate abstracts, from which 17 articles (n = 263,221 patients) met inclusion criteria. Fourteen (82%) studies reported persistence rates, ranging from 16.0% to 93.7%. Seven (41%) studies reported adherence rates, ranging from 15.1% to 99%. Five (29%) studies (n = 416 patients) collected original data on reasons for discontinuing SCIT, of which inconvenience was most cited. All studies were Oxford level of evidence 2b and of good (n = 10) to fair (n = 7) quality. CONCLUSION: Real-world SCIT persistence and adherence rates are poor, with the majority of included studies reporting rates <80%; however, they range widely, explained in part by inter-study differences in measuring and reporting adherence-related findings. Future studies on SCIT adherence may benefit from following concordant definitions of persistence and adherence in addition to standardized reporting metrics.

Magnetic Resonance Imaging as a Diagnostic and Research Tool in Patients with Olfactory Dysfunction: A Systematic Review.

BACKGROUND: Patients with acquired, idiopathic olfactory dysfunction (OD) commonly undergo magnetic resonance imaging (MRI) evaluation to rule out intracranial pathologies. This practice is highly debated given the expense of MRI relative to the probability of detecting a treatable lesion. This, combined with the increasing use of MRI in research to investigate the mechanisms underlying OD, provided the impetus for this comprehensive review. OBJECTIVE: The purpose of this systematic review was to both assess the utility of MRI in diagnosis of idiopathic OD and to describe MRI findings among mixed OD etiologies to better understand its role as a research tool in this patient population. METHODS: A literature search of PubMed, Embase, Cochrane, Web of Science, and Scopus for studies with original MRI data for patients with OD was completed. Studies exclusively investigating patients with neurocognitive deficits or those studying traumatic or congenital etiologies of OD were excluded. RESULTS: From 1758 candidate articles, 33 studies were included. Four studies reviewed patients with idiopathic OD for structural pathologies on MRI, of which 17 of 372 (4.6%) patients had a potential central cause identified, and 3 (0.8%) had an olfactory meningioma or olfactory neuroblastoma. Fourteen studies (42.4%) reported significant correlation between olfactory bulb volume and olfactory outcomes, and 6 studies (18.8%) reported gray matter volume reduction, specifically in the orbitofrontal cortex, anterior cingulate cortex, insular cortex, parahippocampal, and piriform cortex areas, in patients with mixed OD etiologies. Functional MRI studies reported reduced brain activation and functional connectivity in olfactory network areas. CONCLUSION: MRI uncommonly detects intracranial pathology in patients with idiopathic OD. Among patients with mixed OD etiologies, reduced olfactory bulb and gray matter volume are the most common abnormal findings on MRI. Further research is required to better understand the role of MRI and its cost-effectiveness in patients with acquired, idiopathic OD.

Magnetic Resonance Imaging Findings Among Individuals With Olfactory and Cognitive Impairment.

OBJECTIVES: The underlying mechanism of the association between olfactory impairment and dementia may be explained by neurodegenerative changes detected on magnetic resonance imaging (MRI). The purpose of this systematic review is to describe neurodegenerative changes on MRI in patients with olfactory impairment and mild cognitive impairment (MCI) or dementia. STUDY DESIGN: Systematic review. METHODS: A literature search encompassing PubMed, Embase, Cochrane Library, Web of Science, Scopus, and Google Scholar for studies with MRI and olfactory testing among participants diagnosed with MCI or dementia was performed. Sample size, study design, cognitive impairment type, olfactory testing, and MRI findings were abstracted. Two investigators independently reviewed all articles. RESULTS: The search yielded 556 nonduplicate abstracts, from which 86 articles were reviewed and 24 were included. Seventeen (71%) of 24 studies reported hippocampal volume findings, with 14 studies reporting a relationship between hippocampal volume and olfactory performance. Two (50%) of four prospective studies reported the potential utility of baseline hippocampal volume as a marker of dementia conversion from MCI. Five (21%) of 24 studies reporting olfactory functional MRI (fMRI) findings highlighted the utility of olfactory fMRI to identify individuals in the early stages of cognitive decline. CONCLUSION: Current evidence suggests hippocampal volume correlates with olfactory performance in individuals with cognitive impairment, and that olfactory fMRI may improve early detection of AD. However, the predictive utility of these imaging markers is limited in prospective studies. MRI may be a useful modality for selecting patients at high risk of future cognitive decline for enrollment in early treatment trials. Laryngoscope, 132:177-187, 2022.

Association Between Chemosensory Dysfunction and Diet Quality in United States Adults.

BACKGROUND: Evidence suggests chemosensory dysfunction (CSD) patients have altered diet, but population-level evidence assessing diet quality in CSD patients is lacking. OBJECTIVE: We examined the association between CSD and diet quality in a representative sample of United States adults. METHODS: This cross-sectional study included 2831 adults aged greater than 40 years from the 2013-2014 National Health and Nutrition Examination Survey who completed the taste/smell questionnaire and examination. Mean nutrient intake in subjects with self-reported olfactory/gustatory dysfunction (sOD/sGD) and measured olfactory/gustatory dysfunction (mOD/mGD) were compared to those without CSD using univariate Wilcoxon rank-sum tests. The Healthy Eating Index (HEI), a validated measure of diet quality, was calculated. The proportion of subjects with CSD with bottom-quartile HEI was compared to those without CSD using multivariate logistic regression, adjusting for demographic and socioeconomic covariates. RESULTS: The population-weighted prevalence of sOD, sGD, mOD, and mGD was 20.1%, 14.4%, 15.9% and 25.6%, respectively. Subjects with mOD had lower mean intake of total calories, total fat, protein, sodium, and potassium compared to normal subjects (1873.4 ± 49.6 vs 2010.2 ± 24.2 kcal, 72.3 ± 2.7 vs 78.6 ± 1.0 gm, 74.0 ± 2.5 vs 80.4 ± 0.6 gm, 3122 ± 97.2 vs 3353.2 ± 37.0 mg, 2509.8 ± 69.8 vs 2684.7 ± 26.1 mg, P < 0.05 respectively). When controlling for sociodemographic factors and comorbidities, subjects with sOD were more likely to have bottom-quartile HEI compared to normal subjects (OR 1.33, 95% CI 1.04-1.70). CONCLUSIONS: This population-level study suggests an association between poor diet quality and variation in dietary intake in patients with CSD, which warrants further investigation and suggests the possible need for nutritional counseling for CSD patients.

Psychophysical chemosensory dysfunction in eating disorders: a qualitative systematic review.

PURPOSE: Patients with chemosensory dysfunction experience significant quality of life disruptions, including reduced enjoyment of eating. While chemosensory dysfunction has been associated with eating disorders, the relationship is poorly understood. This systematic review aims to characterize psychophysical gustation and olfaction in patients with eating disorders. METHODS: Systematic review of investigations assessing psychophysical chemosensory function in patients with organic eating disorders. RESULTS: 26 studies were included. Five studies assessed both chemosenses, while 12 and 9 assessed exclusively gustation or olfaction, respectively. In total, 779 patients were included [72.4% anorexia nervosa (AN), 26.7% bulimia nervosa (BN), 0.8% combined AN/BN]. Patients with eating disorders experienced rates of hypogeusia up to 87% in AN and 84.6% in BN. There was evidence for alterations in psychophysical olfaction, but orientation of trends were less clear. Chemosensory dysfunction was more evident in AN patients. Treatment correlated with improved chemosensory function. CONCLUSIONS: Despite heterogeneity in study methodology and results, this review demonstrates that patients with eating disorders experience some degree of chemosensory dysfunction, particularly in gustation. This symptomatology overlaps with those experienced by patients with other causes of chemosensory impairment. These findings suggest potential broad psychosocial, dietary, and mental health implications in patient populations experiencing chemosensory dysfunction. LEVEL OF EVIDENCE: Level II.

Gender and authorship trends in rhinology, allergy, and skull-base literature from 2008 to 2018.

BACKGROUND: A recent analysis suggested potential narrowing of the gender gap in research productivity in the field of rhinology. This analysis did not, however, provide insight into how the genders are represented in the rhinologic literature. This study aimed to evaluate 11 years of literature to evaluate for gender differences in authorship position, collaborations, category and content of research, citations, and funding to gain perspective on how gender and authorship has changed over time. METHODS: Authorship data for all articles on rhinologic subject matter published between January 1, 2008 and December 31, 2018 in four otolaryngology journals was collected. The gender of authors was determined by protocol. Category and content of research and funding status/source were additionally obtained. RESULTS: Data were collected from 2666 articles. Gender of 14,510 authors was determined. Female authors accounted for 23% of the overall authors and male authors accounted for 77%. Female first authorship increased significantly over time, but there was no change in female senior authorship. The percentage of female authors steadily increased over time, whereas male authorship decreased slightly. Mixed gender teams were shown to be increasing in frequency. Women published more than expected in basic science and allergy and less than expected in skull base. On funded studies, women were significantly underrepresented as senior authors. CONCLUSION: This study represents the first assessment of gender differences in the rhinology literature. Areas where female representation can improve include senior authorship, increased involvement in skull base publications, and increased funding.

Targeted Molecular Therapies in Allergy and Rhinology.

Biologic agents, monoclonal antibodies that target highly-specific molecular pathways of inflammation, are becoming integrated into care pathways for multiple disorders that are relevant in otolaryngology and allergy. These conditions share common inflammatory mechanisms of so-called Type 2 inflammation with dysregulation of immunoglobulin E production and eosinophil and mast cell degranulation leading to tissue damage. Biologic agents are now available for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, eosinophilic granulomatosis with polyangiitis (EGPA), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). This paper summarizes the diagnosis and management of these conditions and critically reviews the clinical trial data that has led to regulatory approval of biologic agents for these conditions.

A Systematic Review and Meta-Analysis of Taste Dysfunction in Chronic Rhinosinusitis.

OBJECTIVES: Patients with chronic rhinosinusitis (CRS) often describe alterations in sense of taste. These complaints have historically been attributed to olfactory dysfunction; however, there is evidence of direct, objective, gustatory disturbances in the setting of CRS that are not thoroughly characterized. This study sought to investigate and summarize gustatory dysfunction experienced by patients with CRS. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases were reviewed following PRISMA guidelines. English language, original studies investigating objective taste in adult patients with CRS were included. A meta-analysis with inverse variance, random-effects model was performed. RESULTS: Of 2750 studies screened, 11 articles with 471 unique patients were included. Patients with CRS exhibit worse gustatory function compared to healthy controls (standardized mean difference 0.94 [95% CI, 0.44-1.45]). Hypogeusia was identified in 32/95 (33.7%) patients from three studies that used methods with a validated definition of hypogeusia. Older age, male gender, and smoking history were associated with taste dysfunction, while objective gustatory and olfactory dysfunction were not correlated. Subjective taste and quality of life measures were also not associated with objective taste. The impact of sinus surgery on objective taste is unclear. CONCLUSION: Approximately 34% of patients with CRS experience hypogeusia. Neither olfactory function nor subjective taste were associated with objective gustatory function. Given the substantial prevalence of taste dysfunction patients with CRS, there is significant potential for growth in understanding of pathogenesis, impact on quality of life, and potential treatment strategies of taste impairment in the CRS patient population. LEVEL OF EVIDENCE: 1 Laryngoscope, 131:482-489, 2021.

Predictors of Completion of Sublingual Immunotherapy.

OBJECTIVES: Sublingual immunotherapy (SLIT) has emerged as an effective treatment alternative to subcutaneous immunotherapy (SCIT) given its improved safety profile and more convenient dosing. However, SLIT still relies on daily dosing for many years to optimize effectiveness. This study sought to investigate factors that influence patient completion of SLIT. METHODS: We performed an institutional retrospective review of patients who received SLIT (2008-2020). Completion was defined as completing at least 36 months of SLIT. Patient demographics and characteristics, including the number of allergens treated, history of asthma and sinus surgery, number of clinic visits, and total time undergoing SLIT, were documented. Multivariate models were used to analyze predictors of SLIT completion. Subgroup analysis was performed among pediatric patients and patients who discontinued SLIT. RESULTS: Of the 404 total patients, 249 (61.6%) discontinued, 47 (11.6%) completed, and 108 (26.7%) were currently undergoing SLIT. The mean duration of therapy was 11.2 months for those who discontinued and 49.4 months for patients who completed SLIT. The odds of SLIT completion were twice as high with each additional clinic visit (P < .001), and twice as high when the dosage was increased during therapy (P = .06). Pediatric patients younger than age 12 with a history of asthma were over five times more likely to complete therapy (P = .045). Patients with more clinic visits (P < .001) and higher associated costs (P = .003) were less likely to be lost to follow-up. CONCLUSION: Increasing the frequency of clinic visits, improving therapy availability, and mitigating concerns about clinical efficacy may increase patient completion of SLIT. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2111-E2115, 2021.

The association of frailty with olfactory and gustatory dysfunction in older adults: a nationally representative sample.

BACKGROUND: Olfaction and gustation are associated with age-related decline. Deficits in these chemosenses have been associated with significant comorbidities. Meanwhile, frailty, defined as a reduced physiological reserve, is well correlated with mortality and worse health outcomes. We sought to analyze a nationally representative patient population to determine the association between chemosensory dysfunction and frailty. METHODS: Cross-sectional analysis of U.S. National Health and Nutrition Examination Survey (NHANES) 2013-2014 was performed, using multivariate logistic regression to examine the association between chemosensory dysfunction and frailty in adults aged ≥40 years (n = 3547). Self-reported olfactory dysfunction (sOD) and gustatory dysfunction (sGD), and measured olfactory dysfunction (mOD) and gustatory dysfunction (mGD) were assessed for all participants. Frailty was operationalized using a 39-item frailty index (FI) and stratified into 4 groups using validated cutoffs. RESULTS: Participants with sOD and mOD had significantly higher mean FI scores (sOD: 0.18 vs 0.13, p < 0.001; mOD: 0.20 vs 0.14, p < 0.001), whereas subjects with sGD, but not mGD, had higher mean FI scores (sGD: 0.21 vs 0.13, p < 0.001; mGD: 0.14 vs 0.14, p = 0.953). Multivariate logistic regression demonstrated frail participants had significantly greater odds of sGD (odds ratio [OR] 4.11; 95% confidence interval [CI], 3.46 to 4.88), sOD (OR 2.35; 95% CI, 1.98 to 2.78), and mOD (OR 1.58; 95% CI, 1.22 to 2.05), but not mGD (OR 1.21; 95% CI, 0.91 to 1.61). This association was strongest in the frailest group. CONCLUSION: Self-reported chemosensory dysfunction and mOD are independently associated with measures of frailty, suggesting a novel method to assess or predict frailty.

Primary Immunodeficiency and Rhinosinusitis.

Refractory rhinosinusitis can be related to comorbid medical conditions, including primary immunodeficiency. Given the prevalence of immunodeficiency, clinicians should have a low threshold to consider these diagnoses. This article reviews primary immunodeficiencies contributing to chronic rhinosinusitis, including a proposed diagnostic work-up and the evidence for treatment in this unique population.

Predictive value of olfactory impairment for cognitive decline among cognitively normal adults.

OBJECTIVE: Dementia affects over 47 million people worldwide. Olfactory impairment (OI) is a well-established predictive marker of conversion to dementia among those with mild cognitive impairment. This systematic review aims to describe the predictive value of OI for future cognitive decline among cognitively normal adults. METHODS: A literature search encompassing PubMed, EMBASE, and Cochrane for longitudinal cohort studies following cognitively normal adults with baseline OI in comparison to those without OI reporting incident cognitive impairment or dementia was included. Study design, participant demographics, olfactory testing method, and incidence of cognitive decline or dementia were abstracted. Two investigators independently reviewed all articles. RESULTS: The search yielded 964 nonduplicate abstracts and titles, from which 19 full-text articles were reviewed and 10 were included. Studies included were all good quality (mean score 8.7 of 9), and all studies (100%) found a statistically significant association between baseline OI and incident cognitive decline compared with normosmic controls. CONCLUSION: The existing literature suggests that OI predicts future cognitive decline among cognitively normal adults, supporting olfactory evaluation as a low-cost, minimally invasive, and widely available screening tool to be used in combination with other tests to identify adults at early risk of dementia. LEVEL OF EVIDENCE: NA Laryngoscope, 130:840-847, 2020.

The association between diabetes and olfactory impairment in adults: A systematic review and meta-analysis.

BACKGROUND: Evidence suggests that olfactory impairment (OI) may be a degenerative neurologic complication of diabetes; however, the association is not yet well established. The objective of this work was to systematically review existing literature on the association between diabetes and OI in adults, with meta-analysis of evaluable studies. METHODS: A literature search encompassing 358 abstracts from the last 75 years in PubMed, EMBASE, and Cochrane was performed. English-language articles investigating adults with diabetes and OI in comparison to control groups with original data and ≥7 subjects were included. The Newcastle-Ottawa scale was applied for quality assessment. Two investigators independently reviewed all articles. For meta-analysis, the odds ratio of OI in diabetes compared with control groups was calculated using the fixed effects model. RESULTS: The initial search yielded 358 abstracts, from which 21 articles were reviewed and 11 articles (n = 6,747) were included. Studies included were case-control (64%) or cross-sectional (36%) with evidence level 3b. On the Newcastle-Ottawa scale, the mean quality assessment score for case-control and cross-sectional studies was 7.4 (maximum of 9) and 7.0 (maximum of 10), respectively. A statistically significant association between diabetes and olfaction compared with controls was found in 6 (55%) of the 11 articles. Four studies were eligible for meta-analysis, which yielded an overall odds of having OI with diabetes as 1.58 times more likely than in control groups (95% CI [1.16, 2.16]; I 2 = 10.3%). CONCLUSIONS: The reviewed studies support a significant association between diabetes and OI. Further studies are warranted to characterize this association. LEVEL OF EVIDENCE: 3a.